for standing by. We welcome you to Syndax's 4th Quarter and End of Year 2018 Earnings Call. At this time, all participants are in a listen only mode. Later, we will conduct a question and answer session and instructions will follow at that time. As a reminder, this conference call may be recorded.
I would now like to turn the conference over to Melissa Forst with Argo Partners. Please go ahead.
Thank you. Welcome and thank you to those of you joining us today for Syndax's Q4 2018 full year financial and operating results conference call. Joining us this afternoon for prepared remarks will be Doctor. Briggs Morrison, Chief Executive Officer and Rick Shea, Chief Financial Officer. Also joining us on the call today for the question and answer session are Michael Metzger, President and Chief Operating Officer Doctor.
Michael Myers, Chief Medical Officer and Doctor. Peter Ordentlich, Chief Scientific Officer. This call is being accompanied by a slide deck that has been posted on the company's website. So I'd please ask you to turn to the forward looking statements on Slide 2. Before we begin, I would like to remind you that any statement made during this call that is not historical is considered to be forward looking in nature per the Private Securities Litigation Reform Act of 1995.
Actual results may differ materially from those indicated by these statements as a result of various factors, including those discussed in the Risk Factors section of the company's most recent annual report on Form 10 ks as well as other reports filed with the SEC. Any forward looking statements represent the company's views as of today, March 7, 2019 only. A replay of this call will be available on the company's website, www.syndax.com, following the call. And with that, I am pleased to turn the call over to Doctor. Morrison.
Thank you very much, Melissa, and thank you to everyone who is joining us on today's call and webcast. As we closed out 2018 and entered 2019, we took the time to look back at what this management team has accomplished over the past 3.5 years. Our goal has been to build a pipeline of opportunities that would allow us to reach our mission, that would allow us to realize a future in which people with cancer live longer and better than ever before. And as we were closing out 2018, we concluded that we have too many opportunities for a company of our size and resources. And so through conversations with physicians, scientists, advisers and members of our Board, we've prioritized our portfolio.
The work was difficult. We've had many passionate advocates inside and outside our company for every one of our active programs. And we believe that all our active programs have potential to benefit patients. And yet, we had to choose the ones we thought had the most potential. Today, I'm going to share with you the results of that prioritization effort and explain our reasoning.
Slide 3 provides a high level summary of our prioritization effort. As we progress through 2019, we'll be focusing our resources on 2 incredibly exciting opportunities. First, we are anticipating a positive readout of E2112, our Phase III trial of entinostat in hormone receptor positive breast cancer and the subsequent filing of our first NDA and the corresponding launch of our first product. I want to emphasize that a positive OS trial in hormone receptor positive HER2 negative breast cancer would be a landmark result that will be transformative for Syndax and its shareholders. We believe the entinostat opportunity in hormone receptor positive breast cancer carries blockbuster potential.
This is an important opportunity for us, and it will require our focus and resources. 2nd, we anticipate a second quarter filing of the IND for SNDX-five thousand six hundred and thirteen, our potential 1st and best in class targeted agent for the treatment of mixed lineage leukemias, along with the rapid initiation of our broad 5,613 clinical program. As we continue to learn more about the potential of 5,613 in acute leukemia, we see this molecule becoming an additional and important value driver for our company. We may have early clinical data from the program later this year. We believe that the breadth of indications we will investigate with SNDX-five thousand six hundred and thirteen represents a second completely distinct blockbuster opportunity.
This, too, is an important opportunity for us, and it will require our focus and resources. Given these two tremendous opportunities, we've chosen not to move forward at this time with our entinostat KEYTRUDA combination trial in non small cell lung cancer. It's a very difficult decision for us given the strong data we have seen in our ENCORE-six zero one program in both non small cell lung cancer and melanoma. And yet, we believe our near term focus on E2112 and 5,613 is the right thing to do for our company. I will also note that we announced today that neither ENCORE 602 nor 603 met their primary endpoint.
These results were not a material in our decision to refocus our resources, and I will say more later about why we don't think the results of 602603 inform our view of the non small cell lung cancer and melanoma results. Let me now turn to Slide 4 and give you an update on our Phase III trial of entinostat in hormone receptor positive HER2 negative breast cancer, the first area of focus for 2019. Slide 4 again summarizes the trial design. The trial randomized 608 patients to exemestane plus placebo versus exemestane plus entinostat, and the focus of this trial is now clearly and unequivocally on overall survival. As we've noted before, OS interim analyses are done approximately every 6 months, so the next interim OS analysis will be around May November of this year.
Positive outcome at any of these interim analyses or upon achieving the final number of events needed to conclude the study would allow us to file for regulatory approval based upon the terms of our special protocol assessment with FDA. The final analysis of this trial will be conducted once there are 410 survival events. We don't know exactly when those 410 events will occur. But based upon modeling that we've done, we think that the final analysis could be November of this year, although it could drift into May of 2020. We remain very confident in the possibility that E2112 will achieve a survival benefit and hence our decision to keep our focus on this opportunity.
Recall that it was the Phase II OS results that led to the granting of the breakthrough therapy designation by FDA. And as I have summarized previously, based on the results of the Phase II trial, combined with the statistical design of E2112, we always believe the OS endpoint was more likely to be positive than PFS in E2112. Hence, the fact that PFS did not achieve the very high pre specified statistical hurdle does not in any way diminish our confidence in the possibility of achieving a survival benefit in E2112. We also know that OS is the most valued endpoint for patients, physicians, regulators and payers, and hence, a positive OS trial would enable both rapid regulatory review and potentially payer access. Slide 5 emphasizes the blockbuster potential for the entinostat exemestane regimen to be the preferred agent after a CDK4six therapy for hormone receptor positive HER2 negative breast cancer.
We know that CDK4six therapies, most notably Ibrance, are being used increasingly as first line agents, but there's a clear desire to understand what therapies will be affected in a patient who has stopped responding to a CDK4six inhibitor. Our current estimate is that between 30% 50% of patients in E2112 will have received a CDK4six inhibitor prior to entering the trial, and thus, we will have a highly relevant data set in the post CDK4six patient population. This population of patients is relatively large, with an estimated 34,000 patients each year who go on to receive hormone after failing first line therapy and could therefore potentially be eligible to receive entinostat. We're also very excited about the upcoming IND filing for our genetically targeted agent, SNDX-five thousand six hundred and thirteen, and I would therefore like to spend some time describing that program for you now. Slide 6 points out the similarity between our Menin program and other medicines that have been developed to attack fusion proteins that are result of chromosomal rearrangements.
The first example of a recurring chromosomal rearrangement in oncology was the so called Philadelphia chromosome, which results in the BCR ABL fusion protein and which led to the development of Gleevec and other BCR ABL inhibitors. Since then, there have been additional examples where scientists have been able to develop medicines that specifically attack such fusion proteins that result from a chromosomal translocation, including medicines against EML4 ALK fusions, NTRK fusions and RET fusions. These fusion proteins, which are the result of a chromosomal translocation, have been a very fruitful area of oncology drug development given the strong evidence that the fusion protein is driving the cancer cell. Development of such medicines is enabled by being able to precisely define the patients, leading to large treatment effects in specific patient populations in a rapid clinical development and regulatory path. I want to emphasize that our Menin program is an example of a targeted therapy that is designed based upon our understanding of a specific chromosomal rearrangement that leads to a specific fusion protein known to drive the leukemic process.
Slide 7 shows a simplified view of the MLLr fusion protein. The left half of the fusion protein comes from a protein called MLL1, and the right half of the fusion protein comes from another protein. The fusion protein never appears in a normal cell. It is only found in leukemic cells. The left half of the fusion protein binds to a protein called menin, and our drug blocks that binding and hence blocks the ability of the fusion protein to work.
This has studied at the crystal structure level as shown on the right panel of this slide. MENA interaction is shown schematically on Slide 8. On the left figure, you can see that the MLL1 fusion protein bound to menin, assembling a large multiunit machinery that causes abnormal production of a variety of proteins that cause leukemia. On the right figure, you can see that SNDX-five thousand six hundred and thirteen blocks the ability of the fusion protein to bind to menin and stops the abnormal production of the downstream proteins that cause leukemia. The cancer cell then normally differentiates and dies.
I want to again emphasize that 5,613 is targeted to inhibiting the action of a specific fusion protein found only in cancer cells, which is like other medicines that have been designed to work against cancer specific fusion proteins. On Slide 9, we summarize the status of this program. The IND is on track to be filed in the Q2 of this year with the Phase III clinical program to begin soon thereafter. We will be enrolling adults with MLLr leukemias, followed by children with MLLr leukemias. We'll also be enrolling adults with NPM1 mutant leukemia based upon very compelling preclinical data showing SNDX-five thousand six hundred 13 has promising activity in that disease as well as was recently presented at ASH this past December.
I want to emphasize we see a rapid and straightforward clinical development path for SNDX-five thousand six hundred and thirteen, like the path taken for patients with NTRK fusions or IDH1 mutations. We expect that the molecule should have single agent activity, and it's quite possible we could observe clinical activity very early in the clinical development path, again, unlocking significant value for Syndax and its shareholders. As we continue to learn more about the potential of 5,613 in acute leukemia, we see this molecule becoming an additional and important value driver for our company. We therefore have chosen to focus our resources on developing this targeted therapy as rapidly as possible. Let me now turn to our ENCORE clinical trial program in which we've tested entinostat in combination with PD-one pathway antagonists, either PD-one antibodies or PD L1 antibodies.
I'll remind investors that this program was set up as a signal seeking program exploring different tumors that have different immunologic characteristics. We've also invested in looking for biomarkers that could predict clinical benefit. With today's announcement of the results of ENCORE 602 in triple negative breast cancer and ENCORE 603 in ovarian cancer, we have now essentially completed the signal seeking program. Slide 10 shows the immunologic environment is quite different in different tumors, with lung cancer and melanoma often being infiltrated with T cells, colorectal cancer and triple negative breast cancer being characterized as having T cells, but for some reason, they organize around the rim of the tumor and are excluded and ovarian cancer being generally characterized with an absence of T cells. We asked whether entinostat would enhance the activity of PD-one pathway antagonists in these different clinical settings based upon a variety of preclinical observations.
It appears that the beneficial effect of entinostat is evident in the inflamed tumors and not in the other immunologic settings. I think this is an important conclusion of our work. Slide 11 summarizes our findings. We've seen a strong signal of clinical benefit when entinostat is combined with KEYTRUDA in patients with non small cell lung cancer, whose disease has progressed after both chemotherapy and the PD-one antagonist. We've also identified a biomarker, the peripheral blood classical monocytes, that appears to predict clinical benefit in this population of patients.
In addition, we've seen a strong signal of clinical benefit when entinostat is combined with KEYTRUDA in patients with melanoma, whose disease has progressed after both a PD-one inhibitor and a CTLA-four inhibitor. Updates on both of these exciting programs will be presented at AACR. Indeed, we've been notified that each of these will be the subject of an oral presentation. Based on the data in our ENCORE studies, we previously communicated our intention to initiate a registration study in a biomarker defined subset of non small cell lung cancer patients, the ENCORE 607 study. And we believe the ENCORE 601 data also warrants moving forward in melanoma.
We will be reviewing the updated data to be presented at AACR with our partners and remain open to partnering opportunities with entinostat in both non small cell lung cancer and melanoma. However, as a result of our prioritization efforts, we've decided to defer the initiation of the non small cell lung cancer 607 study as well as any melanoma registration study pending the results of E2112. Rick will discuss the impact of this decision on our financial guidance. Let me now briefly turn to Slide 12 and SNDX-six thousand three hundred and fifty two, our potential best in class monoclonal antibody therapy targeting the CSF1 receptor. As you may recall, the monotherapy multiple ascending dose study in cancer patients is ongoing as is the combination of 6,352 with Imfinzi, AZ's PD L1 inhibitor.
And we anticipate selecting a randomized Phase II dose next quarter. Our chronic GvHD trial is also underway, and we anticipate initial efficacy data from that trial in the second half of the year. Finally, Slide 13 summarizes how the transactions that we have completed to acquire both SNDX thousand three hundred and fifty two and SNDX-five thousand six hundred and thirteen prove that we have an ability to strategically expand our pipeline. Our management team and Board have established relationships that allow us to identify quality, differentiated assets, and the extensive clinical development experience of our team gives us a competitive advantage in closing agreements. We continue to expand significant effort in this area, and we consider this capability to be a core strength of our company.
And with that, I'll turn it over to Rick for the financial update.
Thank you, Briggs. The results of our operations for Q4 and full year 2018 and the comparison to the prior year periods are included in our press release, so I won't repeat them in these remarks. Additional financial details are available in our Form 10 ks, which we have just filed this afternoon. Turning to Slide 14, we ended 2018 with $80,900,000 in cash and 26,800,000 shares outstanding. The net change in cash for Q4 was a decrease of $8,700,000 The operating cash burn of $14,800,000 was offset by $6,100,000 of net proceeds from our ATM.
We currently have $31,000,000 available to sell off the ATM. Looking ahead, Slide 14 shows our updated financial guidance for both Q1 and for the full year of 2019. For the Q1 of 2019, we expect R and D expenses to be $11,000,000 to $13,000,000 and total operating expenses to be $15,000,000 to $17,000,000 which includes approximately $1,500,000 of non cash stock compensation expense. For full year 2019, we expect R and D expenses of $46,000,000 to $50,000,000 and total operating expenses of $60,000,000 to $64,000,000 Operating expenses for 2019 are expected to include non cash stock compensation expense of $6,000,000 and interest income runs approximately $2,000,000 so our net cash burn for 2019 is expected to be $52,000,000 to $56,000,000 This projected cash burn for 2019 is approximately $8,000,000 lower than our previous guidance due to the pause in initiating entinostat IO registration studies in either non small cell lung cancer or in melanoma, as Briggs discussed, and to further focusing our operating activities on our highest priority programs. Our current cash, along with reduced spending, will allow us to operate the company to achieve key milestones for our prioritized programs, specifically OS results for E2112 and early proof of concept for SNDX-five thousand six hundred and thirteen, our targeted menin inhibitor.
So now I'll turn the call back over to Briggs.
Thanks very much, Rick. I'd like to close our call with a clear summary of our company priorities. We believe that a positive OS result in 2,112 would be transformative for Syndax and create significant shareholder value. Although we believe the final OS readout for E2112 could occur by the end of this year, we are prepared for a potential later final readout in mid-twenty 20. We're also very excited about the prospects for SNDX-five thousand six hundred and thirteen, our menin MLLr inhibitor.
We the clinical development path, again, unlocking significant value for Syndax. We are prepared to get through the initial proof of concept data from this program, which could take us into mid- to late 2020. We remain extremely excited about our data in lung cancer and melanoma. Updates from both of those programs will be the subject of oral presentations at AACR. However, we believe it is prudent to pause our further development spending in IO until such time that we receive the positive results of E2112.
Rick has outlined our financing plans, and we want investors to be clear that we are not currently forecasting registration programs in lung cancer or melanoma in our financial guidance. For SNDX-six thousand three hundred and fifty two, we remain on track to select a recommended Phase II dose in solid tumors in the Q2 of this year and anticipate having initial efficacy data in chronic GvHD later in the year. Finally, we continue to aggressively look for additional molecules or technologies to bring into our portfolio. I believe we have a proven track record of delivering on this pillar of our strategy, and I believe this is a core strength of our company. As always, I would like to thank the team here at Syndax, our collaborators and most importantly, the patients, trial sites and investigators involved with our clinical programs.
With that, I'd like to open the call for questions.
Thank you. And our first question comes from the line of Christopher Marai with Nomura Instinet. Your line is now open.
Hi, thanks for taking the question. I was wondering if you could help elaborate a little bit on the recommended Phase 2 dose data that we might be seeing for 6,350 2 in combo with PD L1. What other data are you going to provide there beyond a recommended Phase 2 dose? Will you also look at target engagement measures, other measures around sort of the, I guess, patient tumor microenvironment, etcetera? And then I have a follow-up.
Right. So Chris, this is Briggs. The I think you've probably seen some of the PKPD data that we presented from the normal healthy volunteers. We'll be confirming that in the combination trials with PD-one and the recommended Phase II dose. So I think that's the main output.
And Chris, we'll certainly
be presenting data on both PK as well as important PD parameters such as CSF1 levels, IL-thirty four levels, target engagement, monocyte depletion. Those all go into a determination of what the appropriate RP2D is.
Great. That's very helpful. And then I guess just another one, if I may. Regarding the path forward for some of the entinostat IO programs, I understand they're on hold. And I guess that's sort of pending the results of entinostat in breast cancer.
In the event that entinostat does not produce an OS result in breast cancer, would you be open to reopening reevaluating these programs, and to just have specifically in the IO programs or not? How should we sort of think about that? Thank you.
Yes. So I think, Chris, our base assumption is that based on the strong Phase II data that 2,112 will be positive. So we haven't really given too much guidance around what would happen if that wasn't the case and what we would do with the IO program.
Okay, got it. Makes sense. Thank you very much.
Thank you. And our next question comes from the line of Chris Shibutani with Cowen.
For 5,613, look forward to you guys introducing that into the clinic. Can you help us a little bit frame the opportunity? In particular, you talked about potential best in class and the absence of treatment. So could you just give us a sense for the AML rearranged as well as the NPM1 leukemias? What kind of percentage we believe of the AML populations these may be?
And then when you're thinking about the initial monotherapy use, what line or what stage of clinical treatment are these patients that you're thinking about in these initial Phase III work that you're doing? Thanks.
Yes. Hi, Chris. So again, I think you nicely laid out there is essentially 3 different populations that we've been talking about. There's the MLLr rearranged leukemias that occur in kids, which is generally ALL And then there's the mixed lineage leukemias that occur in adults, which is roughly which is generally AML. For the pediatric ALL, the worldwide incidence is probably about 1,000 patients a year, about 10% of ALL.
If you've ever heard of an infant being born with ALL, about 80% of those are these MLLr rearranged leukemias. So that's the pediatric ALL. In adult AML, it's about 6% to 10% of AML, about 5,000 patients a year. The NPM1 mutant population represents about onethree of all AML. So that gives you some rough numbers around the size of the opportunity.
In terms of the patient population that we would study, of course, we'd be studying relapsedrefractory patients in, again, pediatric MLLr rearranged leukemias, adult MLLr rearranged leukemias and adult NPM1 leukemias.
So you make two statements on the Slide number 9, potential best in class. Can you help us understand what data you've seen so far be it preclinical or anything early that would support how you're defining that? And then the fast to market, we're certainly seeing in the AML so much development of novel treatments over the last 3 to 5 years or so? You talk about standard screening protocols. So in existence already are these mutations that are being screened for?
Sure. So again, I think we're only aware of one other molecule that is approaching the clinic for this particular target. We really like our molecule. We think it's very clean, very specific, very potent and hence the hypothesis that it could be best in class. I think that what was your second question?
So potential fast to market potential, you talk about standard screening. Is that in part of this today?
Yes. So I think the short answer is yes. NPM1 mutations are standardly screened for in patients leukemia. And the MLLr, again, it's a chromosomal rearrangement. So whether you do even just a chromosomal spread or you do look specifically for it, these are identified today.
So what we've heard from all of our investigators, again, these will be relapsedrefractory patients, but they know at the time the patients are diagnosed that they have these genetic lesions. And so we don't think we'll have much problem identifying the patients that would be candidates for our therapy.
And in terms of
the background therapy, you say potential monotherapy benefit. Would we assume that these patients are not getting some of the standard, for instance, 7 plus 3 chemo in the AML setting? Or just clarify a little bit more what you mean by monotherapy?
Right. So these would be relapsed refractory patients. So for AML, we would anticipate that they would have been treated with 7 and 3. And for the MLLr AMLs, they tend not to stay in remission very long, so they'll be have relapsed. We wouldn't be at all surprised if they hadn't received, other therapies that are available, whether it's a FLT3 inhibitor, venetoclax, other things that are around for AML.
So that's all up to the physician. They could come in just having relapsed from their 7 and 3 or some re induction regimen, but they would be relapsed refractory patients. And again, I think from a single agent point of view, it's really what we're looking for is clinical activity as a single agent in patients who have relapsedrefractory disease. Not that different from what I think Agios did with their IDH1 inhibitor.
And our next question comes from the line of Robert Hazlett with BTIG. Your line is now open.
Hi, thanks for the question. This is actually Jay Colby on the line for Bert. I was just wondering what will give you the confidence to resume development of entinostat PD-one combinations?
Yes. So I think I Jay, thanks very much for your question. This is really a sort of prioritization effort given the resources that we have available to us. So it's not that we don't have confidence. And as I said, it's kind of interesting that we have 2 oral presentations at AACR.
So obviously, the organizers there thought that we had some pretty interesting data. So it's not that we don't have confidence. I mean, it's really just a prioritization around our resources. So if I should say when 2,112 is positive, if we had more resources, we would go back and revisit these potential investments. But at this point, they're not in our financial guidance.
Great. Okay. That's helpful. And then I guess on 5,613, how should we think about kind of trial size and maybe any other kind of comments you can make on potential trial design here? And then kind of how would you define showing proof of concept for the program?
Thank you.
Sure. So I won't say too much more about the details of the trial. I think after the IND is approved and we have a clear agreed upon detailed trial design, then we'll talk more about it. I think from in the AML space, the standard definition of efficacy is a complete response. So we're looking for patients to have complete responses from their AML.
And again, I think if you look at the Agios story as a good surrogate for the kind of program we'd like to envision.
Thank you.
Thank you. And our next question comes from the line of David Lebowitz with Morgan Stanley. Your line is now open.
Thank you very much for taking my questions. Would you be able to, I guess, help run us through the reason why the entinostat PD-one combos might work in inflamed tumors in a better way than excluded versus non inflamed?
Yes. David, thanks very much for the question. I'll let Peter Rodentlich take that question, our Chief Scientific Officer. Peter?
Yes. Thanks for that question. So we think based on what we've learned, and we'll actually show some of this at AACR, that there's some preexisting priming or some type of immune activity required in order to see benefit with entinostat. And based on some of the gene expression work that we've done, particularly in the lung cancer cohort, we have some better understanding of what some of those resistance pathways may be and some of the way that entinostat may be able to inhibit those. And it just seems that in these harder to treat tumors where the immune activity in general seems to be low like ovarian and triple negative that we just may not have that pre existing signal for which entinostat may be able to work on.
I think that's reflected by the relatively low efficacy of the immune checkpoints overall in those types of tumors. So I think it's a combination of existing resistance pathways that entinostat can target as well as some preexisting immune reactivity.
Thank you very much for that. And I guess, could you if you could just run us back through, I know E2112 OS is coming up, the next analysis. Based on what occurred in the Phase II trial, what is the, I guess, a similar timeframe that as far as OS analyses that the Phase III could theoretically conclude?
Yes. So I think briefly, the trial could conclude at this upcoming readout in May or it may require going to the full 4 10 events. I think we're at that point in the evolution of the trial. Remember that there are also futility analyses, which the trial has continued to progress. So based upon that, it could be as early as May or it may take to the final 410 event.
Thank you. And our next question comes from the line of Joel Beatty with Citi. Your line is now open.
Hi, thanks for taking the questions. The first one is about the focus on your pipeline. It looks like based on the press release, the emphasis is on E2112 trial as well as the menin program. And I noticed the CSF1R program is not on that list. So could you maybe help us understand the difference in focus you see from the early stage CSF1R program compared with your focus on the menin program?
Yes. Joel, thanks so much for the question. Again, I think when we look at the, we like both programs, the CSF1R program, the single agent work being done in GVHD will continue. There's not really new work that we or new resources we have to dedicate to that program. It doesn't not a large burden of our existing resources.
I think as we gear up for 5,613, that is new resources that we want to make sure we have in place and that people have a focus. So and again, as I sort of indicated in my prepared remarks, these diseases that are driven by chromosomal translocations tend to be quite fruitful. So we just want to really make sure we keep our focus on the Menin program. I think if we see activity in GVHD, we'll again reevaluate the prioritization. I think the prioritization work that we do is ongoing constantly as new data becomes available.
So I think that's might help you in thinking about the decisions we've made.
I appreciate it. And another program on the E2112 trial, still some uncertainty on when it will read out. And I imagine that part of what affects that is the P values that are remaining compared with what's already been spent. Could you help us understand that and how what P also has left and how it's split among the remaining potential readouts?
Yes. I don't think we've ever disclosed how the P value gets what the thresholds are at each of the interim analyses, what we can say is that the you may remember the trial was set up where 0.00 2 of the alpha went to PFS and 0.048 goes to OS. There is a very small amount of alpha that's spent on each of the interims, but we've never talked about what the actual threshold is for each of those interims.
Okay. Got it. And maybe one last question on partnering. It sounds like it's still an important focus for looking for additional assets. Could you help us maybe just on a high level, what you're looking for, what would make one potential asset more attractive than another?
Yes. So I always joke with my team that the only molecules we want to license in are ones that work. So if it works, we'd be interested in it. So I think we have a sort of a prioritization list of sort of how we think about different molecules. And sort of interestingly, we set that prioritization list up a number of years ago when we first joined the company.
And tumors that are driven by chromosomal rearrangements and no infusion proteins was actually number 1 on our list. And that's why we were so excited when the MEDIM program became available. So there are a variety of targets that we would be interested in, But I don't think I'd say much more than that.
Got it. Thank you.
Thank you. And our next question comes from the line of Madhu Kumar with R. W. Baird. Your line is now open.
Yes. Thanks for taking my questions. So, first one, thinking about E2112, so you previously talked about preclinical data for CDK4six drugs, their pretreatment not affecting entinostat plus exemestane response to this. So kind of thinking about the flip side, you examined whether later line chemotherapies in HR positive breast cancer respond differently after entinostat plus exemestane treatment versus exemestane alone?
I don't think Peter, do you the only place we'll be able to look at that was in the Phase II data. And I don't know either Peter or Michael, if you know the answer to that.
We didn't preclinically, those experiments haven't been done as to what happens to those types of therapies after treatment with entinostat. In the Phase II clinical trial, that was looked at in terms of the balance of the immediate post treatment as well as overall post treatment therapies, and those were quite well balanced. But the actual response to those individual therapies was not captured. So we don't know how they did. We just know what they got.
Okay. And then thinking about 5,613, a really kind of simple basic science question. What does the meaning of MLL1 interaction do in normal tissues? Does that biology inform potentially relevant PD biomarkers?
Yes. So MLL1 actually is not that the normal MLL1 protein is not that widely expressed in adult tissues. It tends to be involved in embryonic hematopoiesis. So that actually is one of the other reasons why there may be some specificity here because that amino terminus interacts with men and at least the MLL1 interaction you don't see very much in adult tissues.
Okay. So then kind of based on the known kind of interaction based transcriptional effects, is there anything that biology would inform kind of a good biomarker to show the drug setting the target in patients?
Yes. Maybe, Peter, do you want to talk a little bit about that?
Yes. No, happy to. It's a great question and one obviously that we're interested in. And there's been some very nice work published both with menin inhibitors as well as knockdowns of MLL1 or deletions of the N terminus. And those all point to certain gene expression signatures, of which several are highlighted and published on the HAWKS and the MACE I and others involved in hematopoietic differentiation.
And so those all potentially represent genes of interest to look at as well as differentiation markers as well as chromatin modifications that are mediated by these complexes. But obviously, it's a good question and one that's top of our mind as we set up the development to look for these types of assays.
Okay, great. Thanks for taking our questions.
Thank you. And our next question comes from the line of Harshita Polishetty with B. Riley FBR. Your line is now open.
Hi, good afternoon and thank you for taking my questions. So in regards to your menin inhibitor as a follow-up to the questions that have been asked, this has been historically difficult to target due to the protein protein interaction. Briggs, you touched up on the mechanism of action for this molecule in the opening remarks as well as the market opportunity in earlier questions. But I wanted to kind of take a step back and was hoping to gain further insight on the historic failures and challenges with targeting menin and how 5,613 addresses these challenges? And if you have any early insight on the differences between yours and Kura's candidate?
Thanks.
Yes. Harshita, thanks very much for your question. I will say when I first heard about the program and someone told me they had a small molecule that disrupted protein protein interactions, I was as skeptical as you are. Obviously, it's not a very standard thing. What's interesting here is that there are nice crystal structures of the actual amino terminus of MLL1 binding to menin.
It turns out to be a very small 4 or 5 amino acid contiguous segment that sits in the pocket of menin. So it's been well characterized at the crystal structure level and turns out to be highly druggable. So I think it is and again, we'd be happy to send you some of the references. I think it is one of those protein protein interactions that actually are eminently druggable. And I think we have very good preclinical data to show that.
I think the question on how our molecule compares to the cure molecule, we don't know exactly which molecule they are taking to the clinic. So I think it's a little premature for us to comment on that. We really like our molecule. We're excited about the program. We'll sort of, of course, be watching them carefully.
But I think at this stage, it's a little bit hard to know how to compare them.
Great. That helps a lot. Thank you, Briggs.
Thank you. And our next question is a follow-up question from Naray with Nomura Instinet. Your line is now open.
Hey, thanks for taking the follow-up. Just on the menin program, I was wondering, obviously, given the pediatric population that's impacted by these diseases, what's your plan for bringing the molecule into peds versus adults? And how should we expect that to progress as you progress the compounds for the clinic?
Yes, Chris. So our we are extremely interested in the pediatric population. As I said, MLLr ALL is a really unfortunate disease for these little kids. And so we're working hard on pediatric formulation that would allow us to dose both kids and infants. And as part of our discussions, we're trying to lay out a plan that would allow us to move relatively rapidly and seamlessly from initial Phase I trials in adults into the pediatric population.
We'll say more about that, of course, once the IND is approved, and we have an agreement from FDA on what that program will look like. But certainly, that's our anticipation at this point.
Thank you. And I show no further questions at this time. I would like to turn the call back over to Doctor. Morrison for closing remarks.
Great. Thank you very much, everybody, for joining us on the call. If you have any additional questions, we'd be happy to take them, and we look forward to further communications from the company. Thanks again.
Ladies and gentlemen,